View source for CFU-E

{{short description|Progenitor cell to a red blood cell}}

The term '''CFU-E''' ('''Colony Forming Unit-Erythroid'''<ref>{{Cite journal|last1=Miller|first1=Cindy L.|last2=Dykstra|first2=Brad|last3=Eaves|first3=Connie J.|date=2008|title=Characterization of Mouse Hematopoietic Stem and Progenitor Cells|journal=Current Protocols in Immunology|language=en|volume=80|issue=1|pages=22B.2.1–22B.2.31|doi=10.1002/0471142735.im22b02s80|pmid=18432636|issn=1934-368X}}</ref>) denotes a [[hematopoietic stem cell]] in the [[bone marrow]] which eventually matures into a [[red blood cell]] (also called an ''erythroid cell''). It arises from [[CFU-GEMM]] (via BFU-E,<ref name="pmid7553874">{{cite journal |vauthors=Wu H, Liu X, Jaenisch R, Lodish HF |title=Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor |journal=Cell |volume=83 |issue=1 |pages=59–67 |date=October 1995 |pmid=7553874 |doi= 10.1016/0092-8674(95)90234-1|doi-access=free }}</ref> which stands for "erythroid burst-forming units"<ref name="pmid8703820">{{cite journal |vauthors=Marley SB, Lewis JL, Goldman JM, Gordon MY |title=Abnormal kinetics of colony formation by erythroid burst-forming units (BFU-E) in chronic myeloid leukaemia |journal=Br. J. Haematol. |volume=93 |issue=4 |pages=878–83 |date=June 1996 |pmid=8703820 |doi= 10.1046/j.1365-2141.1996.d01-1738.x}}</ref>) and gives rise to [[proerythroblast]]s.

[[File:Wiki CFU-e.png|thumb|Mouse CFU-E colonies stained on Day 3 with Diaminobenzidine for hemoglobin]]

==Murine CFU-E assay==

CFU-E is a stage of erythroid development between the BFU-E stage and the pro-erythroblast stage. CFU-E colony assay is designed to detect how many colony-forming-units of erythroid lineage there are in a hematopoietic tissue (bone marrow, spleen, or fetal liver), which may be reflective of the organism’s demand for oxygen delivery to the tissues or a hematopoietic disorder.

Early erythroid progenitors are found at a quite low frequency relative to later stages of erythroid differentiation, such as the pro-erythroblast and the basophilic erythroblast stages which can be detected by flowcytometry directly ex-vivo.<ref>{{Cite journal|last1=Socolovsky|first1=Merav|last2=Nam|first2=Hyung-song|last3=Fleming|first3=Mark D.|last4=Haase|first4=Volker H.|last5=Brugnara|first5=Carlo|last6=Lodish|first6=Harvey F.|date=2001-12-01|title=Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts|url=https://doi.org/10.1182/blood.V98.12.3261|journal=Blood|volume=98|issue=12|pages=3261–3273|doi=10.1182/blood.V98.12.3261|pmid=11719363 |issn=0006-4971|url-access=subscription}}</ref> Furthermore, unlike for the pro-erythroblast and later stages of erythroid development, no truly reliable and unique positive flow-cytometric markers exist, though it is possible to use negative exclusion markers to deplete a cell population of other precursors and differentiated cells by cell sorting, thus greatly enriching it for the CFU-E activity.<ref>{{Cite journal|last1=Terszowski|first1=Grzegorz|last2=Waskow|first2=Claudia|last3=Conradt|first3=Peter|last4=Lenze|first4=Dido|last5=Koenigsmann|first5=Jessica|last6=Carstanjen|first6=Dirk|last7=Horak|first7=Ivan|last8=Rodewald|first8=Hans-Reimer|date=2005-03-01|title=Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E)|journal=Blood|volume=105|issue=5|pages=1937–1945|doi=10.1182/blood-2004-09-3459|issn=0006-4971|doi-access=free|pmid=15522951 }}</ref> CFU-E cells express Epo receptor, c-Kit (Stem cell factor receptor), [[transferrin receptor]] (CD71+), and are Ter119(glycophorin-A associated antigen)-negative. For the above reasons, the CFU-E assay, as inefficient and variable as it can often be, is still in use today.

Cells at the CFU-E stage express some [[erythropoietin receptor]] (EpoR), and thus can be induced to terminally differentiate in vitro in 2–3 days in the presence of only [[erythropoietin]] (Epo) (together with the basic contents of culture media: FBS, BSA in IMDM). Methylcellulose is a semisolid media additive that allows an investigator to stain (with diaminobenzidine reagent for hemoglobin) and then count individual colonies, each arising from a single plated progenitor that is at the CFU-E stage. By day 2 from the time of plating, each CFU-E colony will contain between 8 (minimum) and 64 hemoglobinized cells most of which are in their end-stage of erythroid differentiation. It is possible to see a small spectrum of hemoglobinization level and possibly cell size, indicating that some cells in the colony have achieved the end-stage faster than others.

Cell number in a colony is important because pro-erythroblast stage is also Epo-responsive (expresses Epo receptor), but the proliferative capacity of these cells is not as high, thus yielding a colony with fewer than 8 cells. Likewise, an earlier stage of erythroid differentiation may also yield colonies in Epo-only medium, but these colonies would likely be smaller and/or not hemoglobinized, since the stages before the CFU-E stage (MEP and BFU-E) require other factors (IL-3 etc) and more time for growth that will also delay the terminal differentiation and hemoglobinization.

==References==
{{reflist}}

==External links==
* {{MeshName|CFU-E}}

{{Blood physiology}}

[[Category:Blood cells]]
[[Category:Colony forming units]]